By establishment of the hybridoma method by Kohler and Milstein (1975), it has been made possible to fuse antibody-producing B cells incapable of conducting persistent culture with myeloma cells capable of conducting persistent culture thereby to produce continuously growing B cell hybridoma while producing antibody (Kohler et al., Nature, 256, 495, 1975). Using this method, many monoclonal antibodies which react with desired antigens have been produced. Further human monoclonal antibodies have also been produced by transformation of lymphocytes using EBV (Epstein-Barr virus), etc., in addition to cell fusion between human lymphocytes and mouse myeloma cells or human myeloma cells.
Monoclonal antibodies to malignant tumor cells are utilized for basic investigations such as analysis of tumor antigens, etc. In addition, clinical applications including serological diagnosis, radioimaging of tumor using labeled antibodies, administration of antibodies having anti-tumor effect in vivo, etc. have also been attempted gradually.
At present, cancer therapy has been made synthetically by combining surgical therapy, chemotherapy, radiotherapy, immunotherapy, etc. These therapies are also freely applied to lung cancer but relapse due to local and remote metastasis is not unusual so that lung cancer is unfavorably prognostic among cancers. Under such circumstances, it is indispensable to produce monoclonal antibody to lung cancer, from an aspect of new specific immunotherapy adds to the treatments of lung cancer. Mention may be made of monoclonal antibodies capable of reacting with human lung cancer in, for example, Published Unexamined Japanese Patent Application Nos. 60-58926 and 60-199830, EP-156578-A, EP-155172-A.
However, anti-lung cancer monoclonal antibodies currently produced as above are mouse monoclonal antibodies which are produced by hydriboma obtained by cell fusion of antibody-producing cell of a mouse immunized by human lung cancer cell lines and mouse myeloma. These mouse monoclonal antibodies are foreign matters to human so that they are unsuited for direct administration in the living body and it has been desired to produce human monoclonal antibody having high reactivity.
Among methods for producing human monoclonal antibodies currently attempted, the human-human hybridoma method involves disadvantages that human myeloma cells having a good fusion efficiency comparable to mouse myeloma cells have not been established yet, stable antibody-producing clones are obtained only with difficulty even by the EBV method, handling and separation of virus are difficult, etc. Further the production of monoclonal antibody to human lung cancer cells by the human-mouse heterohybridoma method has not been succeeded on a full scale.